Reference : Identification of the active gene coding for the metastasis-associated 37LRP/p40 mult...
Scientific journals : Article
Human health sciences : Oncology
Life sciences : Multidisciplinary, general & others
Life sciences : Genetics & genetic processes
Life sciences : Biochemistry, biophysics & molecular biology
Identification of the active gene coding for the metastasis-associated 37LRP/p40 multifunctional protein.
Clausse, Nathalie [Université de Liège - ULiège > > > > Laboratoire de recherche sur les métastases > >]
Jackers, Pascale [Université de Liège - ULiège > > Laboratoire de recherche sur les métastases > >]
Jares, P. [Université de Liège - ULiège > > > > Laboratoire de recherche sur les métastases > >]
Joris, Bernard mailto [Université de Liège - ULiège > > Centre d'ingénierie des protéines > >]
Sobel, Mark E. [National Cancer Institute - NCI > > > > Molecular Pathology Section > >]
Castronovo, Vincenzo mailto [Université de Liège - ULiège > > Laboratoire de recherche sur les métastases > >]
DNA & Cell Biology
Mary Ann Liebert, Inc.
Yes (verified by ORBi)
[en] Amino Acid Sequence ; Amino Acids ; Animals ; Base Sequence ; Chickens ; Cloning, Molecular ; Gene Dosage ; Genes/genetics ; Humans ; Molecular Sequence Data ; Neoplasm Metastasis ; Protein Precursors/chemistry/genetics ; Protein Structure, Secondary ; RNA, Messenger/analysis ; Receptors, Laminin ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Transcription, Genetic/genetics
[en] A 37LRP/p40 polypeptide is of major interest because it is consistently up-regulated in cancer cells in correlation with their invasive and metastatic phenotype. Furthermore, this polypeptide presents intriguing multifunctional properties because it has been characterized as the precursor of the metastasis-associated 67-kD laminin receptor (67LR) and as a cytoplasmic ribosomal-associated protein. The isolation of the 37LRP/p40 gene is a prerequisite for identifying the molecular mechanisms responsible for the constant up-regulation of the 67LR expression in cancer cells. To date, the active 37LRP/p40 gene has never been identified in any species due to the existence of multiple pseudogenes in most vertebrates genomes. In this study, we report for the first time the gene structure and potential regulatory sequences of the 37 LRP/p40 gene. The chicken genome was selected to undergo this characterization because it is the only known vertebrate that bears a single 37 LRP/p40 gene copy. The 37 LRP/p40 active gene is composed of 7 exons and 6 introns and bears features characteristic of a ribosomal protein gene. It does not bear a classical TATA box and it exhibits several transcription initiation sites as demonstrated by RNase protection assay and primer extension. Analysis of potential regulatory regions suggests that gene expression is driven not only by the 5' genomic region but also by the 5' untranslated and intron 1 sequences. On the basis of gene structure and extensive protein evolutionary study, we found that the carboxyterminal domain of the protein is a conserved lock-and-key structure/function domain that could be involved in the biosynthesis of the higher-molecular-weight 67-kD laminin receptor in vertebrates, whereas the central core of the protein would be responsible for the ribosome associated function. The first identification of the active 37LRP/p40 gene presented in this study is a critical step toward the isolation of the corresponding human gene and the understanding of the molecular mechanisms involved in the up-regulation of its expression during tumor invasion and metastasis.
Association contre le cancer; Association sportive contre le cancer; European Biomed; FRSM; Centre Anti-Cancéreux; Grant de la communauté française de Belgique
"Etude de la famille mutigénique codant pour la protéine PRL37/p40"
Researchers ; Professionals ; Students

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